The causes of depression in the elderly are poorly understood. Genetic factors appear to be less significant in patients presenting with depression for the first time in later life. In addition, the concept that psychological and social factors are the primary contributors to the occurrence of depression in later life though intuitively appealing is not well supported by available evidence. Thus at least in late onset depression, other factors may play a significant role in addition to genetic and social factors. There has been considerable speculation that structural changes in the brain are of primary importance in the aetiology of late onset depression. Recent studies utilizing magnetic resonance imaging have demonstrated an increased incidence of deep white matter and subcortical gray matter (hyperintensities) changes in patients with late onset depression. The NIH consensus development conference noted that one of the most promising questions for future research is the clarification of the relationship between subcortical brain abnormalities. depressive and cognitive symptomatology. and early versus late onset depression in the elderly. Hypertension, diabetes, cardiovascular disease appear to be risk factors for the deep white matter and subcortical hyperintensities. These hyperintensities have varied pathology. The pathology varies according to the site, size, and shape of the hyperintensities. We propose to study elderly late onset depressives, early onset depressives, and controls using a cross sectional design to evaluate the relationship between the hyperintensities, cognitive impairment, onset of depression and depressive symptoms. In order to reduce setting bias and to include a broad range of patients, patients from both inpatient and outpatient settings will be studied. If the relationship between late onset depression and these structural changes is confirmed, it has many implications for treatment and potentially for prevention of disease. The role of risk factors for hyperintensities and the need to better treat/prevent these factors becomes more critical. It also provides a basis for understanding the neuroanatomy of depression.